This application for the treatment of type 2 diabetes mellitus in children (T2DM) is from a strong cadre of investigators from Children?s Hospital of Pittsburgh and the University of Pittsburgh. These investigators bring together a long-standing tradition of expertise in 1) childhood diabetes (Drs. Arslanian and Becker), 2) in investigating insulin resistance and secretion in children (Dr. Arslanian, PI), 3) in behavioral medicine and lifestyle intervention for childhood obesity (Drs. Marcus and Vinditti), 4) in physical activity and lifestyle interventions (Drs. Kriska and Aaron), 5) in epidemiology of chronic disease and large intervention trials of obesity, type 2 diabetes and cardiovascular disease (Drs. Lewis Kuller, Kriska and Marcus), and 6) in recruiting for large intervention trials (Janet Bonk). Based on our collective strength, we believe that we can fully meet the goals for a clinical site for this multicenter trial of type 2 diabetes mellitus in children. The PI, Silva Arslanian, M.D., has been at the forefront of the "emerging epidemic" of type 2 diabetes in children. She has been a consultant to the NIH, CDC, and the American Diabetes Association (ADA). She was one of the eight-member panel of experts who developed the ADA Consensus Position of type 2 Diabetes in Children and Adolescents. Her research in childhood insulin resistance and secretion has made important contributions to the understanding of risk factors for type 2 diabetes mellitus in children. In addition, there is a strong institutional infrastructure to support our application, including 1) the pediatric General Clinical Research Center (Director, Silva Arslanian, M.D.), 2) the Diabetes Center at Children?s Hospital of Pittsburgh, 3) the NIH-funded Obesity Nutrition Research Center (ONRC), (David Kelley, M.D., PI), 4) the Graduate School of Public Health, and lastly, 5) the multiple collaborations with different disciplines including national programs for disadvantaged youth. Finally, the K24 Award of the PI in patient-oriented research complements one of the objectives of this RFA which is to train and develop young clinician-scientists. Our proposal will investigate intervention strategies in youth with T2DM with the objective of delaying beta-cell deterioration and preserving beta-cell function. To this aim we propose to use a randomized clinical trial design with 3 arms: conventional care, behavioral lifestyle and risk management intervention, and behavioral lifestyle intervention combined with dual-agent insulin sensitizing therapy. Measures of beta-cell function and insulin resistance will be the primary outcome of interest. Urinary albumin excretion and carotid artery intima-media thickness will be the secondary outcomes of interest. We also propose that this RFA incorporate ancillary studies. A comprehensive approach to therapeutic interventions in children with type 2 diabetes mellitus will form the basis for prevention of adult morbidity and mortality starting early in childhood.